Researchers from England and Japan have recently fully clarified the
mechanism
of fatigue, known as central fatigue, implicated in Chronic Fatigue
Syndrome. Dr. Eric Newsholme, from Oxford University, and Dr.
Takanobu Yamamoto, from Tezukayama University, have made numerous
research discoveries about fatigue and the mechanisms that define
it.

For starters, there are at least five metabolic causes of
fatigue that have been reported in the medical literature. These
include 1) a decrease in the phosphocreatine level in the muscle, 2)
a proton accumulation in the muscle, 3) depletion of the glycogen
store in muscles, 4) hypoglycemia and 5) an increase in the plasma
concentration ratio of free tryptophan to branched-chain amino
acids.

"Central fatigue" is of keynote importance here due to the fact
that it has been implicated in clinical conditions such as Chronic
Fatigue Syndrome (CFS) as well as Post-Operative fatigue.
Central fatigue is defined as fatigue in the central nervous system
(CNS). The implications are important because the fatigue in CFS is
central fatigue, in other words, fatigue in the central nervous
system (CNS)! According to these researchers, fatigue in the CNS
results from fatigue that occurs in a large portion of intercerebral
control circuits caused by suppression in the level of voluntary
exciting, which are suppressed in the number of motor units to the
level of voluntary neuromuscular junction - muscle fibers and the
firing frequency. In other words, CFS fatigue is a fatigue different
from the fatigue in the motile muscles themselves. Moreover, these
researchers have found that this fatigue is different from the so
called tiredness feeling caused by physical (muscular) fatigue and,
in fact, is generated in a state that is not accompanied by physical
fatigue. This is something most of us hadn't read previously!

Dr. Newsholme has been researching central fatigue mechanisms
for over twelve years. Along with Dr. Yamamoto, these
researchers have now fully clarified the mechanism for central
fatigue in the CNS. They found that specific inhibitors of the
L-system transporter on the blood-brain barrier (BBB) make it
possible to suppress the fatigue in the CNS. Furthermore, two
components were found to be therapeutically effective in suppressing
this CNS fatigue. The first was a lab based research chemical known
as BCH. However, the second component was one that is readily
available. That component was branched-chain amino acids otherwise
known as BCAA's. BCAA's are essential amino acids for the human
body. BCAA's are made up of a mixture of three individual amino
acids that include L-leucine, L-isoleucine and L-valine which have a
branched-chain in its carbon chain. BCAA's are commonly used
supplements by bodybuilders.

In a nutshell, these researchers proved that by inhibiting the
L-system transporter, experiments verified that BCAA's and/or BCH
suppressed the uptake of tryptophan thereby alleviating fatigue in
the central nervous system and thus improved endurance capacity in
the animals tested. Research has proven that fatigue in the CNS
doesn't show a reduction in the serotonergic system function in the
central and peripheral nerves but, in contrast, an enhanced nerve
transmission response and this implies a relation to a change in the
transmission of extracellular fluid 5-HT (5-hydroxytryptamine) that
depends on an increase in tryptophan.
This change in the transmission of extracellular fluid 5-HT causes
suppression in the surrounding brain nerves, resulting in fatigue in
the CNS. This is the basis for the tryptophan/5-HT hypothesis. The
fatigues in both of the central system (CNS) and the peripheral
system (muscle system) exist in a related manner. The tryptophan,
which is a causal substance of the fatigue, is transferred from the
peripheral system (in blood) to the central system (brain) through
the blood-brain barrier (L-system transporter) to give inhibiting
(negative) information to the CNS. In other words, an excessive
amount of tryptophan or 5-HT in the brain suppresses the CNS, causes
a reduction in the motor system output that is released through
pyramidal tracts and x-motor neurons. This causes inhibition of
animal treadmill running performance. It is this mechanism that
causes the fatigue phenomena (central fatigue) derived from the CNS.
For all CFS patients, this is much more than just "being tired!"
Most importantly, however, is the fact that this scientific research
may have vital clinical implications for CFS patients due to the
applicability of BCAA's.